Sample pre-compression valve for liquid chromatography

ABSTRACT

A sample pre-compression valve for liquid chromatography applications is described. The valve enables a sample pre-compression while the solvent pump continues to conduct solvent to the chromatography column. Furthermore, the sample pre-compression valve includes an INJECT position, a LOAD position and a PUMP PURGE position, in which all connecting grooves of the valve are flushed with liquid. A use of the sample pre-compression valve is described as part of a sampler for liquid chromatography applications.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation under 35 U.S.C. § 120 and claims thepriority benefit of co-pending U.S. application Ser. No. 17/481,203[Attorney Docket No. TP105691CON3], filed Sep. 21, 2021, which is acontinuation under 35 U.S.C. § 120 and claims the priority benefit ofco-pending U.S. application Ser. No. 16/852,287 [Attorney Docket No.TP105691CON2], filed Apr. 17, 2020 now U.S. Pat. No. 11,156,590, whichis a continuation under 35 U.S.C. § 120 and claims the priority benefitof co-pending U.S. application Ser. No. 15/959,848 [Attorney Docket No.TP105691CON1], filed Apr. 23, 2018 now U.S. Pat. No. 10,634,652, whichis a continuation under 35 U.S.C. § 120 and claims the priority benefitof co-pending U.S. application Ser. No. 15/190,570 [Attorney Docket No.TP105691USUTL1], filed Jun. 23, 2016 now U.S. Pat. No. 9,964,527, whichclaims the priority benefit under 35 U.S.C. § 119 to German PatentApplication No. DE 10 2016 101 658.6 [Attorney Docket No.TP105691DESEC1], filed on Jan. 29, 2016, the disclosure of which isincorporated herein by reference.

FIELD OF INVENTION

The present invention relates to a sample pre-compression valve forliquid chromatography applications.

BACKGROUND

In the HPLC, a sample to be analyzed must be fed into a high-pressureliquid flow; meanwhile, any interruption of this flow must be as shortas possible. For this purpose, high-pressure injection valves are usedthat enable a nearly uninterrupted switching of the liquid flow. Such anarrangement is described, for example, in the U.S. Pat. No. 3,530,721 A.

The injection valves currently being used have at least four ports to beable to conduct a sample pre-compression by means of a sample conveyingsystem. An additional port is needed when the solvent contained in thesample conveying system or a sample taken incorrectly is to be discardedthrough a waste port that is connected to the injection valve. A samplerwith a corresponding injection valve is already described in DE 10 2008006 266 A1.

When the solvent is changed in an HPLC system, it is necessary to flushout old solvent in the lines between the solvent bottles and theinjection valve, likewise through the waste port. There is thepossibility here, for example, to run the so-called injection needledirectly over a waste tank and dispose the content of the line by meansof the solvent pump. The disposal is generally referred to as a “purge.”The previously mentioned change of solvent is described, for example, inU.S. Pat. No. 6,129,840 A.

Furthermore, with most of the injection valves in the state of the art,some connecting lines of a sampler are not completely flushed in theso-called injection position (INJECT position), meaning the positionduring which the sample is applied on the chromatography column. Theconnections that are embodied most frequently in the form of grooves inthe stator or rotor of the injection valve are required to enableswitching back and forth between the so-called load position (LOADposition; adding the sample to a sample loop of the injection valve) andthe pressure compensation position (PRESSURE COMPENSATION position;position in which the sample loop is brought to system pressure orambient pressure), yet also to enable switching back and forth betweenthe LOAD position and the PRESSURE COMPENSATION position, withoutinterrupting the solvent flow to the column. The flow must not beinterrupted for the reason as the pump pressure would rise otherwise andthe column pressure would drop enormously. The former is problematic forreasons of safety and the latter requires long equilibration phasesbetween the sample analyses. The solvent that was used in the beginningof the chromatography run (e.g. in the equilibration phase) collects inthe mentioned grooves and falsifies the gradient composition in thefurther course by mixing the solvent residue with the gradient(particularly critical in low-flow/nanoflow applications).

The problem to be solved by the present invention is therefore theprovision of an injection valve with relatively simple arrangement to beused in a sampler for liquid chromatography applications, which can workwith the fewest ports possible and the fewest grooves connecting theports, while having a high density and no areas that are not flushed,and which can furthermore be produced at low cost, while the valveenables a pre-compression without an interruption of the solvent flowfrom the pump to the column arising in the transition from the LOADposition to the PRESSURE COMPENSATION position. Another problem to besolved is to provide an injection valve in which all grooves of thevalve are flushed through completely in the INJECT position.

SUMMARY

The present invention relates to a sample pre-compression valve forliquid chromatography applications, in particular high-performancechromatography (HPLC), which enables a sample pre-compression while thesolvent pump continues conducting solvent to the chromatography column.Furthermore, the sample pre-compression valve according to the inventionenables an INJECT position, a LOAD position and a PUMP PURGE position,in which all connecting grooves of the valve are flushed throughcompletely. The present invention also relates to the use of a samplepre-compression valve according to the invention for production of asampler used in liquid chromatography applications. In addition, thepresent invention also relates to a sampler for liquid chromatographyapplications that includes a sample pre-compression valve according tothe invention.

The invention solves the described problem by providing a samplepre-compression valve for liquid chromatography applications, whichcomprises a ring-shaped stator and a ring-shaped rotor, which arearranged next to each other along their circular surface and which canbe rotated against each other along their circular surface, whereas thestator has at least five ports A, B, C, D and E and the rotor at leasttwo grooves X and Y, whereas the grooves X and Y can connectrespectively two of the ports A, B, C, D and E with each other andwherein the ports can be embodied point-shaped or groove-shaped,characterized in that

(i) the groove X connects the ports A and B with each other in a valveposition 1, in such a way that there are no dead volumes present in thegroove X and so that the groove Y does or does not connect the ports Cand D, and

(ii) the groove X connects the ports A and B in a valve position 2, insuch a way that there are dead volumes present in the groove X and sothat the groove Y does or does not connect ports C and D, and

(iii) the groove X connects the ports A and E with each other in a valveposition 3, in such a way so that there are no dead volumes present inthe groove X and so that the groove Y does or does not connect the portsB and C.

The groove Y preferably connects the ports C and D in position 1 of thesample pre-compression valve according to the invention. It is alsopreferred that the groove Y does not connect the ports C and D inposition 2 of the sample pre-compression valve according to theinvention. It is furthermore preferred that the groove Y connects theports C and B in valve position 3. In this way, it is possible that thesample pre-compression valve according to the invention enables inposition 1 that the sample is added to a sample loop of the injectionvalve (LOAD position); meanwhile also a solvent pump can be connectedwith a chromatography column. In that the groove Y does not connect theports C and D in position 2 but the groove X connects the ports A and B,a so-called PRESSURE COMPENSATION position can be produced, in which thesample loop is brought to system pressure or ambient pressure and thesolvent pump continues to supply the chromatography column. Position 3enables an INJECT position in which the sample is applied on thechromatography column.

The sample pre-compression valve according to the invention is designedin such a way that there are no dead volumes present in the connectinggrooves in positions 1 and 3 (LOAD and INJECT positions).

The term “sample pre-compression” expresses in the word “samplepre-compression valve” the suitability of the valve for samplepre-compression in a sampler used in liquid chromatography applications.

The ring-shaped stator and respectively the ring-shaped rotor arepreferably circular discs that contact each other along their circularsurface and can be rotated against each other along the rotationdirection of their circular surfaces. In other words, the rotor has afront surface that interacts with the front surface of the stator(contacting surfaces of the stator and rotor), on which preferably (atleast) the two grooves X and Y are arranged with which the port openingcross sections of the ports A, B, C, D and E, which are provided on thefront surface of the stator, are connected or blocked respectivelypressure-tight and preferably depending on the rotation position of therotor relative to the stator.

A port can be understood to mean a point-shaped port or groove-shapedport. A point-shaped port is understood to mean a circular hole or acircular recess, whereas a groove-shaped port is understood to mean onethat has a certain extension direction in the stator. If a port is agroove-shaped port, it is preferable according to the invention that thegroove extends along a circular path around the center of thering-shaped stator.

“Dead volumes” is understood to mean a part of a groove that cannot beflushed in one flow in a certain valve position. Vice versa, “no deadvolumes” is understood to mean that essentially all parts of therelevant groove are flushed in a certain valve position.

In one embodiment of the sample pre-compression valve it is preferablethat the ports A and B are arranged on one or two (preferably one)circular path(s) around the center of the ring-shaped stator. However,it can also be preferable according to the invention that port A isarranged at the center of the ring-shaped stator and port B on acircular path around the center of the ring-shaped stator.

In the sample pre-compression valve according to the invention, ports C,D and E can be arranged on one or more (preferably one) circular path(s)around the center of the ring-shaped stator.

In a variant of the sample pre-compression valve according to theinvention, the ports A, B, C, D and E are preferably arranged on thesame circular path around the center of the ring-shaped stator. In afurther variant, the ports B, C, D and E can be arranged on the samecircular path around the center of the ring-shaped stator. In thevariant mentioned last, it can be preferred that port A is arranged atthe center of the ring-shaped stator.

In the following, the sample pre-compression valve according to theinvention will be described by means of two different embodiments, thepreferred characteristics of which, however—to the extent they aretechnically feasible—are transferable to the respective otherembodiment.

In the first embodiment of the sample pre-compression valve it ispreferable that the ports A and B are arranged on one or two (preferablyone) circular path(s) around the center of the stator. It is furthermorepreferred that the stator has an additional port F, besides the ports C,D and E, which is arranged at the center of the ring-shaped stator.Preferably, the ports C, D and E are also arranged on a circular patharound the center of the ring-shaped stator.

In addition, the sample pre-compression valve according to the inventionin the first embodiment can comprise a further groove Z in the rotor,which can connect port F with one of the ports A, B, C, D or E. It isparticularly preferred that the groove Z in position 1 connects theports E and F with each other in such a way that no dead volumes arepresent in groove Z. It is also preferred that the groove Z in position2 connects the ports E and F with each other in such a way that deadvolumes are present in groove Z. Likewise preferred is that the groove Zin position 3 connects the ports D and F with each other in such a waythat no dead volumes are present in groove Z.

In a position 4 of the sample pre-compression valve according to theinvention in the first embodiment, it is furthermore preferred that thegroove X connects the ports D and E with each other in such a way thatno dead volumes are present in groove X. It is also preferable in thisposition 4 that the groove Z in position 3 connects the ports C and Fwith each other in such a way that no dead volumes are present in grooveZ. It is thereby possible with the sample pre-compression valveaccording to the invention to implement a so-called PUMP PURGE position,in which the groove Z is flushed through completely with solvent bymeans of a solvent pump.

With the sample pre-compression valve according to the invention in thefirst embodiment, also a position 5 can be implemented in which thegroove X connects the ports B and C with each other in such a way thatno dead volumes are present in groove X, while the groove Y does or doesnot connect and preferably connects the ports D and E. This position 5facilitates the provision of a sampler with the sample pre-compressionvalve according to the invention, having an INJECT position that is analternative to position 3. In this position, it is furthermore preferredthat the groove Z connects the ports A and F with each other.

In the first embodiment, the ports A, B, C, D and E are preferablyarranged on one single circular path around the center of thering-shaped stator. It is preferred here that all spaces between theports are equally far away from each other.

The groove X is preferably a groove that has at least twocircle-path-shaped sections that are preferably arranged on the samecircular path and connected by one section of the groove that isarranged outside of this circular path.

The groove Y is preferably a circle-path-shaped (arched) groove or aline-shaped groove that can connect two points on the same circularpath.

The groove Z is preferably a hook-shaped groove and preferably designedin such a way that one section of the groove connects the center of thering-shaped rotor with one point on the circular path of the rotor and afurther section of the hook-shaped groove is arranged on said circularpath, meaning it is designed as an arched shape.

In the first embodiment of the sample pre-compression valve according tothe invention it is furthermore preferable that the valve has at mostsix ports. It is furthermore preferred that these at most six ports arearranged in the stator of the valve. It is furthermore also preferredthat the rotor has at most three grooves.

In the second embodiment of the sample pre-compression valve accordingto the invention, it is preferred that port A is arranged at the centerof the ring-shaped stator. In addition, port B is preferably arranged ona circular path around the center of the ring-shaped stator. Likewise,the ports C, D and E are preferably arranged on one or more circularpath(s) around the center of the ring-shaped stator. It is particularlypreferable that the ports B, C, D and E can be arranged on the samecircular path around the center of the ring-shaped stator.

In positions 1 and 2 of the sample pre-compression valve according tothe invention in the second embodiment, the port E is preferablyconnected with none of the grooves X and Y. It is furthermore alsopreferred that the port D is connected with none of the grooves X or Yin positions 2 and 3.

It is furthermore preferred for the sample pre-compression valve in thesecond embodiment that it has at most five ports. The reduction to amaximum of five ports in the second embodiment has the advantage of asimplified arrangement and it reduces the leakage rate compared to aninjection valve with six or more ports.

It is also preferred in the second embodiment that the port A isessentially spaced equally far away from the ports B, C, D and E. Theexpression “essentially” is to clarify that there can only bedifferences in the spacing here that are due to processing technology,which however do not affect the functionality of the injection valve. Itis also preferred that the ports C and E are arranged on opposites sidesrelative to the port A and that both are essentially spaced equally faraway from the ports B and D respectively. The word “essentially” has thesame meaning here as above.

According to the invention, it is also possible that the samplepre-compression valve in the second embodiment has more than twogrooves. However, it is particularly preferred according to theinvention that the valve has at most the two mentioned grooves. Themaximum number of two grooves has the advantage that the leakage rate inthe valve can be kept very low.

The groove X in the second embodiment preferably has a hook-shape,whereas the groove Y is preferably designed line-shaped or arched,whereas the two end points are respectively arranged on a circular patharound the center of the ring-shaped rotor. The two grooves preferablyextend in the direction of the interacting front surfaces of the rotorand stator. The terms “hook-shaped” or “circle-path-shaped” areunderstood in the same way as for the first embodiment.

The sample pre-compression valve according to the invention in thesecond embodiment likewise has a position 4, in which the groove Xconnects the ports A and D with each other in such a way that no deadvolumes are present in groove X. At the same time, it is preferred inthis position 4 that the groove Y connects the ports B and E with eachother.

The sample pre-compression valve according to the invention in thesecond embodiment can also have a position 5, in which the groove Xconnects the ports A and C with each other in such a way that no deadvolumes are present in groove X. In this position, it is also preferablethat the groove Y connects the ports D and E with each other.

The sample pre-compression valve according to the invention in the firstembodiment can also have a position 6, in which the groove X connectsthe ports A and C with each other in such a way that there are deadvolumes present in groove X. In this position 6 it is furthermorepreferred that the ports B, E and D do not have a connection with afurther port. In other words, the groove Y does not connect any of theother ports in this position.

The hook shape of the groove Z in the first embodiment and of the grooveX in the second embodiment, which extends into a circular path in onesection from the central port, has the advantage that the contactsurface between the stator and rotor is moistened during the switchingof the valve. The lifetime of the valve is thereby increased.

The present invention also relates to a sampler for liquidchromatography applications, which comprises, besides the samplepre-compression valve according to the invention, a sample conveyingsystem, a sample loop, a solvent pump, a chromatography column and asample intake/discharge line.

Furthermore, the sampler according to the invention preferably has acontrol unit for actuation of the sample pre-compression valve and thesample conveying system.

The sample conveying system can preferably also be provided with amovable element that is guided sealed in a pump volume and can be movedfor conducting the sample fluid contained in the pump volume by means ofone of the drives of the sample conveying system, which can be actuatedby the control unit.

The sample conveying system is preferably designed high-pressureresistant and can generate pressures that are used in high-performanceliquid chromatography, preferably pressures greater than 500 to 600 bar,preferably maximum pressures greater than 1500 bar.

If the sampler according to the invention has a sample pre-compressionvalve in the first embodiment, it is preferred that port A is connectedwith port D through the sample loop, port B is connected with the sampleconveying system, port C with the sample intake/discharge line, port Ewith the chromatography column and port F with the solvent pump. Thisway, the following functionalities result in positions 1 to 5 for thesampler with the sample pre-compression valve according to the firstembodiment:

Position 1: INJECT position

Position 2: PRESSURE COMPENSATION position

Position 3: LOAD position

Position 4: PUMP PURGE position

Position 5: INJECT position (alternative)

In the LOAD position, the sample can be taken in the sample loop throughthe sample intake/discharge line, in that a certain volume is aspired bythe sample conveying system. This is possible because the grooves X andY and the sample loop connect the sample conveying system with thesample intake/discharge line. For the intake of the sample, the sampleintake/discharge line is led into a sample tank, preferably in that aneedle that is dipped into the sample is seated on the end of this line.While this way, the sample can be drawn up into the sample loop in theLOAD position, solvent can be conducted through the groove Z from thesolvent pump to the chromatography column.

After the LOAD position, the sample pre-compression valve according tothe invention can be brought into the PRESSURE COMPENSATION position, inwhich the solvent pump is still connected with the chromatography columnthrough the groove Z, but in which the port D is closed pressure-tight.The groove X continues to connect the ports A and B, so that pressurecan be built up in the groove X and the sample loop through the sampleconveying system, which pressure equals the later column pressure. Thisis also referred to as the pre-compression, before the valve is broughtinto a switching position and in which the sample can be applied on thechromatography column. During this step, it is furthermore beneficial ifthe needle is brought out of the sample into a so-called wash port atthe end of the sample intake/discharge line.

If the sample pre-compression valve according to the invention in thefirst embodiment is brought into the INJECT position after the PRESSURECOMPENSATION position, pressure equaling or approximating the workingpressure on the chromatography column and respectively the pressure inthe pump line is already present in the PRESSURE COMPENSATION positionfrom the sample pre-compression. In this position, the grooves X and Zenable the solvent pump to conduct the sample including solvent to thechromatography column. In the INJECT position, the sample conveyingsystem, the groove Y and the sample intake/discharge line can be flushedthrough the groove Y, which connects the ports B and C. It is preferredhere that a cleaning pump, flushing the cleaning fluid into the washport through the sample conveying system, the line that connects thesample conveying system with the port B, the groove Y and the sampleintake/discharge line are arranged on the sample conveying system.

The sample pre-compression valve according to the invention in the firstembodiment thereby has the advantage that in all three positions, whichare the LOAD, PRESSURE COMPENSATION and INJECT positions, the pump canconvey solvent (with or without sample) to the chromatography column. Itis possible at the same time to conduct the sample pre-compression inthe PRESSURE COMPENSATION position.

After the INJECT position, the valve can be brought back into thePRESSURE COMPENSATION position, in which the sample loop that is underhigh pressure is connected with the sample conveying system that isunder atmospheric pressure. Since the liquid volume of the sampleconveying system is preferably much higher than that of the sample loop,the connected pressure surge related thereto can be absorbed withoutcomplications. After the decompressing phase of the sample loop by meansof the sample conveying system, the valve can be brought into position 1(equivalent of the LOAD position), in which the remaining pressure canbe let off into the wash port through the sample intake/discharge lineand its needle. After this pressure reduction, the valve is already inposition 1, which is equivalent of the LOAD position and in which asample can be drawn again for a repeated analysis run. For this purpose,the valve itself does not need to be activated, but the needle on thesample intake/discharge line must be taken out of the wash port and ledinto the sample tank. Subsequently, the steps described above can berepeated.

A sampler with a pre-compression valve according to the invention of thefirst embodiment has the following advantages: No pressure drop occurson the chromatography column between the analysis runs. The valve hasmaximum tightness because the grooves are arranged with a greatestpossible spacing between them. A sample pre-compression is possiblebetween the taking of the sample and injection of the sample into thechromatography column. Analysis time can be saved, as a wash phase ispossible during the analysis run. By virtue of the arrangement of thesampler according to the invention, a sample taken incorrectly that isnot supposed to reach the chromatography column can be discarded easily.The idle volume is dependent only on the sample loop and therefore lowand constant. No uncontrolled pressure reduction can occur when thesample conveying system is disconnected from the analysis path. In theLOAD position and in the INJECT position, there are no dead volumes inthe grooves, i.e. all grooves can be flushed. Consecutive switchingstates of the sample pre-compression valve are nearest neighbors so thatno unintended connections occur and the contact travel can be kept low.

The sampler with the sample pre-compression valve according to theinvention in the second embodiment furthermore preferably comprises asample loop with sample conveying system and needle seat, a dischargeline, a solvent pump and a chromatography column. It is preferred herethat port A is connected with the solvent pump, port B connected withthe chromatography column, port C with the sample loop and port D withthe discharge line.

In this arrangement, positions 1 to 6 correspond to the followingstates:

Position 1: LOAD position

Position 2: PRESSURE COMPENSATION position

Position 3: INJECT position

Position 4: PUMP PURGE position

Position 5: FULL PURGE position

Position 6: UNDERPRESSURE position

The sample loop in the sampler according to the invention with thesample pre-compression valve according to the invention in the secondembodiment comprises a first and a second sample loop segment. The firstsample loop segment is preferably connected on one end with the port Eand on the other end with a pump volume of the sample conveying system.The second sample loop segment is preferably connected on one end withthe port C and on the other end with the sample conveying system. Thesecond sample loop segment is preferably an intake part and a feed partdesigned so that it can be split up, whereas in the split state volume,the free end of the intake part connected with the pump can aspire asample fluid, which can be conveyed through the feed part in theconnected state in the direction toward port E.

In the LOAD position, the two ports A and B are connected with eachother so that solvent can be conducted from the solvent pump to thechromatography column. It is preferred at the same time that ports C andD are connected with each other, so that the sample drawn up in theintake part can be injected into the feed part of the sample loop.

According to the invention, the sample pre-compression valve, afteraspiration of the pump volume in the LOAD position, is switched to thePRESSURE COMPENSATION position in which the ports C and E are closedpressure-tight. In the PRESSURE COMPENSATION position, the drive of thesample conveying system is actuated preferably so that pressure buildsup in the closed sample loop and in the pump volume of the sampleconveying system, which is essentially equivalent of the systempressure. Even if before switching the sample pre-compression valve fromthe PRESSURE COMPENSATION position to the INJECT position, the pressurein the sample loop is not identical to the system pressure of thepump(s) but a low pressure difference remains, this low pressuredifference is kept low enough according to the invention, so that thepressure difference cannot have any impermissible negative effects onthe flow through the chromatography column or even lead to damage on theinjection valve or the chromatography column. This applies in the sameway also in the LOAD position of the sampler with injection valveaccording to the invention in the first embodiment.

After the PRESSURE COMPENSATION position, the sample pre-compressionvalve is brought into the INJECT position, in which the solvent pump isconnected via the groove X and the ports A and E with the sample loop,and the port C of the sample loop via the groove Y with the port B ofthe chromatography column in a sampler with sample pre-compression valveof the second embodiment. This way, the sample drawn up by means of thesolvent pump in the feed part of the sample loop can be conveyed to thechromatography column and the analysis run can take place.

Upon completion of the analysis run, the sample pre-compression valve ofthe second embodiment can be brought into the PUMP PURGE position, whichis understood to mean a state in which the feed line is flushed withsolvent from the pump to the port A connected with it, the port A itselfis flushed as well as the groove X between the port A and the port D,and the port D itself, whereby they can be cleaned and solvent can bedisposed of.

After the PUMP PURGE position, the sample pre-compression valve in thesecond embodiment can be brought into a FULL PURGE position, which isunderstood to mean a state in which all grooves and ports of the samplepre-compression valve (with exception of port B that is connected withthe chromatography column), as well as all intake and discharge lines,sample loops and the sample conveying device are flushed with solventpreferably by means of a pump whereby they can be cleaned. Furthermore,also the sample needle from the outside and the injection port can bewashed in the FULL PURGE position of the sample pre-compression valve.For this purpose, the sample needle is extended slightly out of theneedle seat (also referred to as injection port), so that the solventconveyed from the pump will wash away contaminations on the outside ofthe sample needle and on the needle seat. The soiled solvent can thenrun, for example, through an overflow on the needle seat into a wastetank.

In addition, the sample pre-compression valve according to the inventionin the second embodiment enables an UNDERPRESSURE position in a sampleraccording to the invention, in which the groove X preferably connectsthe ports A and C with each other, whereas the ports E and B are closedpressure-tight. This position has the advantage that underpressure inthe sample loop and up to the pump can be created. This underpressurecan be created in that the pump volume of the sample conveying device isincreased, preferably in that a movable element (piston) of the sampleconveying device is moved toward the outside. The creation of theunderpressure helps support the pump when the solvent is aspired, inthat the hydrostatic column of the solvent in the solvent bottles isovercome. The UNDERPRESSURE position furthermore enables enlargingunwanted gas bubbles so that these can be removed from it more easily.

Said designs of the grooves and ports in the sample pre-compressionvalve of the second embodiment of the sampler according to the inventionhave the advantage that all parts of the grooves and ports can beflushed in nearly all switching position (except for the PRESSURECOMPENSATION and UNDERPRESSURE positions). In other words, there arenearly no areas in the injection valve that cannot be flushed, wherebygood cleaning is possible and no modifications in the running behaviorcaused by contaminations occurs in the HPLC operation.

It is furthermore preferable according to the invention that the samplepre-compression valve of the second embodiment has at most the specifiedsix positions, notably the LOAD position, the PRESSURE COMPENSATIONposition, the INJECT position, the PUMP PURGE position, the FULL PURGEposition and the UNDERPRESSURE position, preferably to implement allnecessary states in a sampler for an HPLC. According to the invention,all specified positions can be realized by the two aforementionedgrooves in the injection valve. The sample pre-compression valve in thesecond embodiment of the sampler according to the invention ispreferably arranged in such a way that it can be brought into saidpositions by rotation in the following order: LOAD position→PRESSURECOMPENSATION position→INJECT position→PUMP PURGE position→FULL PURGEposition→UNDERPRESSURE position→LOAD position. This has the advantagethat it can be transitioned directly from the respective switchingposition to the respectively required next switching position, withoutunwanted intermediate switching positions. This does not cause anysample losses, no unwanted mixing with potential residues in the portsthat would otherwise come into contact through the intermediateswitching positions and no unwanted pressure drop occurs.

An additional advantage of the valve arrangement in the secondembodiment of the sampler according to the invention is that, dependingon the switching position of the valves, nearly all existing parts canbe flushed by means of the solvent pump(s). It is therefore furthermorepreferred that the sampler according to the invention has at most one(solvent) pump path. The pump path is understood to mean here theconnection line from the solvent pump(s) to the port A. The sampleraccording to the invention can thus not only comprise one solvent pumpbut also two or more solvent pumps, all of which can supply solvent tothe relevant port. It is preferred according to the invention that thesampler includes no further cleaning pump besides the solvent pump(s),as the cleaning can take place while the solvent is being conveyedthrough the solvent pump(s) by virtue of the different injection valveswitching positions.

The sampler according to the invention with the sample pre-compressionvalve of the second embodiment has the advantage that the integration ofa sample conveying system enables a pressure compensation is created bythe sample conveying system in the split loop while the switchingpositions of the pre-compression valve are changed, if the valve has aPRESSURE COMPENSATION position for this purpose, in which the ports towhich the sample loops are connected are not connected with other portsin the valve.

Under the split loop principle, the sample loop is split in theconnecting part between the sample conveying system, which can bedesigned, for example, as a syringe, and the relevant port of the valve.The end of the intake part connected with the sample conveying system ofthe split connecting part of the sample loop is moved to a sample tankto take in the necessary sample volume or to a flushing medium tank totake in the flushing medium. In the end, the split connecting piece ofthe sample loop is connected again so that the sample volume taken incan be injected into the chromatography column by means of the pump(s)while the injection valve is in the INJECT position. This basicprinciple has already been described in U.S. Pat. No. 4,939,943 A1.

The pressure compensation (pressure increase or pressure reduction) inthe sample loop of the sampler according to the invention with a valveof the first and second embodiment is preferably achieved by means of acorresponding actuation of the sample conveying system drive. This way,no interfering fluid flows arise in the pressure compensation. Thesampler additionally has the advantage that the pump continues to beconnected with the chromatography column in the PRESSURE COMPENSATIONposition. The flow of the fluid through the chromatography column isthereby preserved and no unwanted peaks in the pressure flow can arisein the switching processes.

Furthermore, the FULL PURGE position of the sample pre-compression valveof the second embodiment has the advantage that both the sample loop aswell as port A that is connected to the pump, the two ports C and E thatare connected to the sample loop, the port D and the sample conveyingsystem can be flushed by means of the solvent pump without requiringthat the sampler has an additional cleaning pump. The PUMP PURGEposition has the advantage that the sample pre-compression valve of thesecond embodiment can also have a position in which the port A and theport D that are connected to the solvent pump are flushed.

In all variants of the sampler according to the invention, the sampleconveying system comprises a movable element by means of which thevolume of the sample conveying system can be altered. The movableelement can be designed, for example, as a driven syringe, whereas themovable element is formed by the piston of the syringe.

Once the PRESSURE COMPENSATION position of the respective injectionvalve is reached, the control unit can move the piston and respectivelythe movable element by means of a corresponding actuation of the drive,along a predefined path that is sufficient in order to generate thenecessary alteration of the pump volume of the sample conveying systemthrough elasticities of the devices conducting the fluid and through thecompressibility of the fluid itself, whereas increasing the pump volumecan reach a pressure reduction in the sample loop essentially down toambient pressure and a pressure increase in the sample loop essentiallyto the operating pressure of the pump. The movement of the movableelement can be actuated and respectively controlled.

To enable the pressure regulation or the final pressure during thepressure compensation in the sample loop, a pressure sensor can beprovided that records the pressure of the fluid in the closed sampleloop or in the pump volume of the sample conveying system, at leastduring the time in which the injection valve is in the PRESSURECOMPENSATION position.

In this variant, the signal of the pressure sensor is preferably led tothe control unit, whereas the control unit compares the fluid pressureto the target pressure value and actuates the sample conveying system insuch a way that the pressure of the fluid reaches a high-pressure targetvalue before the injection valve is switched from the PRESSURECOMPENSATION position to the INJECT position and/or so that the fluidpressure reaches a low-pressure target value before the injection valveis switched from the PRESSURE COMPENSATION position to the LOADposition.

The sampler according to the invention with the sample pre-compressionvalve of the second embodiment can preferably have a waste line, whichleads from port D to a tank surrounding the needle seat or to the needleseat itself. According to the invention, the needle seat is one with arinsing function. If the sample needle is slightly driven out of theneedle seat in the FULL PURGE position, the conducted solvent can washoff the sample needle from the outside. At the same time, the needleseat with rinsing function preferably has an overflow from which thesolvent can drain into a waste tank.

Analogously, a sampler with the sample pre-compression valve of thefirst embodiment can have a wash port, in which the needle that isarranged on the sample intake/discharge line can be washed. Here, too,the wash port is designed as a tank into which the needle can be dipped.The wash port comprises a line that can conduct the solvent used forcleaning into a waste tank.

The present invention also relates to the use of a sampler according tothe invention in the liquid chromatography, specifically in thehigh-pressure liquid chromatography. In other words, the presentinvention relates to a method for conducting liquid chromatography inapplication of a sampler according to the invention, in particular bymeans of transitioning the positions of the sample pre-compression valveof the sampler according to the invention in the ways described above.In the use of the sampler according to the invention, the pump(s) forconducting the solvent/fluid is (are) preferably also used as cleaningpump, in particular in the PUMP PURGE position and the FULL PURGEposition, which applies specifically to an injection valve of the secondembodiment.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is explained in more detail by means of two embodimentexamples illustrated in the drawings.

FIG. 1 is a schematic diagram of an HPLC system with a sampler accordingto the invention with a sample pre-compression valve of the firstembodiment in the LOAD position.

FIG. 2 is the HPLC system according to FIG. 1 , whereas the samplepre-compression valve has been switched from the LOAD position to thePRESSURE COMPENSATION position.

FIG. 3 is the HPLC system according to FIG. 1 and FIG. 2 , which hasbeen switched to the INJECT position.

FIG. 4 is the HPLC system according to the foregoing Figures, whereasthe sample pre-compression valve is in the same position as in theINJECT position but where the rinsing phase is shown during the analysisrun.

FIG. 5 is the HPLC system according to the foregoing Figures, whereasthe sample pre-compression valve has been switched to the PUMP PURGEposition.

FIG. 6 is the HPLC system according to the foregoing Figures, whereasthe injection valve is in the PRESSURE COMPENSATION position but thesample conveying system is decompressed (decompression part 1).

FIG. 7 is the HPLC system according to the foregoing Figures, whereasthe sample pre-compression valve is in the position to take the sample(decompression part 2).

FIG. 8 is the HPLC system according to the foregoing Figures, whereasthe injection valve is in an alternative INJECT position.

FIG. 9 is a schematic diagram of an HPLC system with a sampler accordingto the invention with a sample pre-compression valve of the secondembodiment in the LOAD position.

FIG. 10 is the HPLC system according to FIG. 9 , whereas the injectionvalve has been switched from the LOAD position to the PRESSURECOMPENSATION position.

FIG. 11 is the HPLC system according to FIG. 9 and FIG. 10 , which hasbeen switched to the INJECT position.

FIG. 12 is the HPLC system according to the foregoing Figures, whereasthe injection valve has been switched to the PUMP PURGE position.

FIG. 13 is the HPLC system according to the foregoing Figures, whereasthe injection valve has been switched to the FULL PURGE position.

FIG. 14 is the HPLC system according to the foregoing Figures, whereasthe injection valve has been switched to the UNDERPRESSURE position.

FIG. 15 is the HPLC system according to FIG. 13 in the FULL PURGEposition with additional connecting line from the waste port to the washport of the needle seat.

DETAILED DESCRIPTION OF THE EMBODIMENTS

In the following, a sampler according to the invention with apre-compression valve of the first variant is described by means ofFIGS. 1 to 8 .

FIG. 1 shows a schematic diagram of an HPLC system for samples in thenano-liter range with a sampler 10 according to the invention, whichcomprises a sample conveying system 5, a sample pre-compression valve 3and a pump, preferably a high-pressure pump 40. In addition, the sampler10 comprises a sample loop 60, a chromatography column 41, a cleaningpump 57, a return valve 58, and a sample intake/discharge line 59 with asample needle 42 on its end, and a sample tank 43, a solvent bottle 61,a wash port 62 with a waste line 47 leading to the waste tank 63. Thesample pre-compression valve in FIG. 1 is in the LOAD position, in whichthe groove X connects the ports A and B, the groove Y connects the portsC and D and the groove Z connects the ports E and F with each other.Furthermore, the sample needle 42 that is mounted on the end of thesample intake/discharge line 59 is arranged in the sample tank 43. Ifthe piston 53 of the syringe 50 is pulled toward the outside of thesample conveying system 5, the volume V increases and a sample is takenup into sample loop 60 via the connection of the ports D and C via thegrooves X and Y and the sample loop 60. In this position, thechromatography column 41 can be flushed through the connection of theports E and F via the groove Z by means of a solvent pump 40 that isconnected with a solvent bottle 61. The sample loop can be apressure-resistant line with a small diameter, for example, in the formof glass or stainless steel capillaries.

The sample pre-compression valve 3 is preferably comprised of a stator 1and a rotor 2. Whereas, stator 1 is preferably provided with the portsA, B, C, D, E and F. These ports connect the sample pre-compressionvalve 3 with the other functional elements of the HPLC element throughthe connecting lines described above, which can be embodied as capillaryconnections. In the interest of clarity, the high-pressure screwconnections required for this purpose are not shown in FIG. 1 . Forreasons of simplicity, the sample pre-compression valve is shown in theborder area between the stator 1 and the rotor 2, whereas both thedesign of the front face of the stator 1 as well as the design of thefront face of the stator 2 is shown, to help understand the mode offunctioning. Within the sample pre-compression valve 3, the ports arepreferably embodied as drill holes leading to the other side of thestator. The rotor 2 as shown in the illustration of FIG. 1 comprises thegrooves X, Y and Z, which are aligned precisely on the drill holes ofthe entry and exit ports.

The rotor 2 is preferably pressed against the stator with pressingforce, so that a common border area between the rotor 2 and the stator 1is formed where both parts tighten against each other. The pressingforce is dimensioned for this purpose in such a way that the arrangementis still tight even under the highest expected pressures.

The sample conveying system 5 comprises a syringe 50 in the illustratedembodiment, in which a piston 53 is guided pressure-tight and movable.The piston 53 is powered by drive (not illustrated), for example, a stepmotor. The drive is preferably actuated by a control unit (notillustrated). The control unit preferably also controls the switchingprocesses of the sample pre-compression valve 3, which has acontrollable drive that is not illustrated.

FIG. 2 shows the sampler of the invention according to FIG. 1 in thePRESSURE COMPENSATION position, in which the groove Z still connects thesolvent pump 40 with the chromatography column 41 through the ports Eand F, but where the port D is closed pressure-tight, so that a pressurehigher than the ambient pressure can be built up in the sample loop 60via the groove X and the sample conveying system. This way, the pressurein sample loop 60 can be adjusted to the operating pressure on thechromatography column 41. During this step, the sample needle 42 on theend of the sample intake/discharge line 59 can be driven into the washport 62, so that the groove Y and the line 59 with the sample needle 42can be washed in the next step.

FIG. 3 shows the sampler of the invention according to the foregoingFigures with the sample pre-compression valve 3 in the so-called INJECTposition, in which the sample can be conducted from the sample loop 60to the chromatography column 41 not only via the grooves Z and X, but inwhich the sample conveying system 5, the ports B and C, the groove Y,the sample intake/discharge line 59 and the sample needle 42 can also bewashed through the connection of the groove Y of the ports B and C. Thelatter is preferably effected in that a cleaning pump 57 is connected bya return valve 58 to the sample conveying system 5 that flushes solventthrough said components into the waste tank 63.

In the process, preferably also the movable element 53 of the syringe 50of the sample conveying system 5 is used, whereas the movable element 53is pressed into the sample conveying system 5, so that the volume V ofthe sample conveying system 3 is reduced. The latter position is shownin FIG. 4 .

FIG. 5 shows the sampler 10 according to the invention from FIGS. 1 to 4, whereas the sample pre-compression valve 3 is in the PUMP PURGEposition. The groove Z connects the ports F and C here so that thesolvent pump 40 can flush solvent through the groove Z, the sampleintake/discharge line 59 and the sample needle 42 into the wash port 62.During this process, the sample loop 60 is excluded from the flushingprocess.

FIG. 6 shows the sampler 10 according to the invention from theforegoing Figures, whereas the sample pre-compression valve 3 is againin the PRESSURE COMPENSATION position, meanwhile this here is more anillustration of the decompression (part 1), meaning of the pressurereduction in the sample loop by the increase in the volume V of thesample conveying system.

FIG. 7 shows the second part of the decompression, in which the samplepre-compression valve 3 is driven into the same position as in the LOADposition, whereas the movable element 53 of syringe 50 in the sampleconveying system 5 is brought into a position that enables a repeateddrawing up of a sample through the sample conveying system 5 into sampleloop 60. As shown in FIG. 1 , the sample needle 42 must be brought intoa sample tank 43 here from the wash port 62.

In alternative to the INJECT position, the sample pre-compression valveof the second embodiment can also have an alternative INJECT position,which is shown in FIG. 8 . Here, the groove X connects the ports B andC, whereas the groove Y connects the ports D and E, while the groove Zconnects the ports A and F. It is also possible in this way to conductsolvent from the pump 40 via the grooves Y and Z through sample loop 60to the chromatography column 41, while the sample conveying system 5,the groove X and the sample intake/discharge line 59 as well as thesample needle 42 can be cleaned.

In the following, a sampler according to the invention with a samplepre-compression valve of the second variant is described by means ofFIGS. 9 to 15 .

FIG. 9 shows a schematic diagram of an HPLC system with a sampler 10working according to the split-loop principle, which comprises a sampleconveying system 5, an injection valve 3 and a pump, preferably ahigh-pressure pump 40. In addition, the sampler 10 is provided with asample loop that consists of the first connecting piece 51 and a secondconnecting piece 52, 44. This can be a pressure-resistant line withsmall diameter, for example, in the form of glass or stainless steelcapillaries. The connecting piece 51 is connected with a port E of thesample pre-compression valve 3 and with the sample conveying system 5and respectively its pump volume V. The second connecting piececonsisting of an intake part 44 and a feed part 52 is designed so thatit can be disconnected. For this purpose, the feed part 52 ends in aninjection port 45, which is connected with the port C of the samplepre-compression valve 3 through the feed part 52. The intake part 44connected on one end with the pump volume V of the sample conveyingsystem 5 is provided on the other end with a sample needle 42, wherebythe intake part 44 can be connected with the injection port 45.

The sample needle 42, however, can also be moved to a sample tank 43 andfrom there, aspire a defined sample volume into the intake part 44 inthe manner explained in the following. Furthermore, the sample needle 42can also be moved to a tank for a cleaning fluid (not illustrated), inorder to take in cleaning fluid from it into the sample conveying system5. When the sample needle 42 is reinserted into the needle seat 45, thecleaning fluid that has been taken in through the sample loop part 51,the port E, the groove Y and the port B, which is connected withchromatography column 41, can be transported to the chromatographycolumn when piston 53 is pressed down, for the reason that port C isclosed pressure-tight (FIG. 12 ). This way, the chromatography column 41can be cleaned. This cleaning procedure is conducted preferably in thePUMP PURGE position of the sample pre-compression valve, which is shownin FIG. 12 .

The sample conveying system 5 comprises a syringe 50 in the illustratedembodiment, in which a piston 53 is guided pressure-tight and movable.The piston 53 is powered by means of a drive 55, for example, a stepmotor. The drive is preferably actuated by a control unit (notillustrated). The control unit preferably also controls the switchingprocesses of the sample pre-compression valve 3, which has acontrollable drive that is not illustrated.

The port D of the injection valve is preferably connected with a wasteline 47 from which a fluid can be discharged into a waste reservoir thatis not illustrated.

The high-pressure pump 40 is connected with the port A of the samplepre-compression valve. A chromatography column 41 is connected with theport B.

The sample pre-compression valve 3 is preferably comprised of a stator 1and a rotor 2. At the same time, the stator 1 is preferably providedwith the ports A, B, C, D, and E. These ports connect the samplepre-compression valve 3 with the other functional elements of the HPLCelement through the connecting lines described above, which can beembodied as capillary connections. In the interest of clarity, thehigh-pressure screw connections required for this purpose are not shownin FIG. 9 . For reasons of simplicity, the sample pre-compression valveis shown in the border area between the stator 1 and the rotor 2,whereas both the design of the front face of the stator 1 as well as thedesign of the front face of the stator 2 is shown, to help understandthe mode of functioning. Within the sample pre-compression valve 3, theports are preferably embodied as drill holes leading to the other sideof the stator. The rotor 2, as shown in the illustration of FIG. 9 ,comprises at least the grooves X, and Y, which are precisely aligned onthe drill holes of the entry and exit ports.

The rotor 2 is preferably pressed against the stator with pressingforce, so that a common border area between the rotor 2 and the stator 1is formed where both parts tighten against each other. The pressingforce is dimensioned for this purpose in such a way that the arrangementis still tight even under the highest expected pressures.

In the LOAD position of valve 3 as shown in FIG. 9 , the grooves X and Yare aligned with the ports A, B, C, D and E so that the groove Yconnects the port C with port D and the groove X connects the ports Aand B. In this LOAD position, the high-pressure pump 40 can thus conductfluid in the direction toward chromatography column 41. The port E ispreferably closed pressure-tight in the process. In this LOAD position,the sample can furthermore be drawn up from a sample tank 43. It ispossible in addition that the sample needle 42 is driven into a sampletank 43. By moving the piston 53 upward, meaning out of the sampleconveying system 5, for example, from the position A into position C(see FIG. 9 ), the sample from the sample tank 43 can be taken up thereinto the sample needle 42 and possibly also into the sample loop 44. Thesample needle 42 can then be moved out of the sample tank 43 into theinjection port 45 for injection after completed pressure compensation.

In the next step, the pressure in the sample loop is then adjusted tothe system pressure of the chromatography column 41, meaning to thepressure with which the high-pressure pump 40 feeds the fluid to theinlet of the chromatography column 41. For this purpose, the samplepre-compression valve 3 is switched to a PRESSURE COMPENSATION positionin which the connecting piece 51 and the second connecting piece or thefeed part 52 of the sample loop are preferably not connected to theother ports of the sample pre-compression valve (FIG. 10 ).

In order to adjust the pressure in the sample loop 52, 44, 51 includingthe sample conveying system 5 to the system pressure, the piston 53 ofthe high-pressure resistant sample conveying system 5 can be moved outof position C into position B. So not to interrupt the flow through thechromatography column 41 while the volume required for the compressionof the sample loop content is conducted, the groove X in the rotor 2 ispreferably designed hook-shaped, so that the two ports A and B are alsostill connected while in the PRESSURE COMPENSATION position. Theconveying path of the piston 53 from position C to position B that isnecessary for the pressure build-up can be calculated based on thecompressibility of the fluid volume trapped in the sample conveyingdevice 5 and the sample loop, and by the elasticity of the arrangement,and the current pump pressure. In alternative, the pressure compensationcan be achieved by means of a control circuit for the pressure in thehigh-pressure resistant sample conveying system. For this purpose, thepressure must be measured at a suitable point and the position of thepiston 53 in the sample conveying system 5 must be set in such a way bythe drive 55, so that the pressure equals the necessary target pressure(=column pressure). For the pressure measurement, a pressure sensor orindirectly, a force measurement can be used. A force measurement on thepiston 53 or in the drive 55 are feasible solutions. Once pressureequivalence is reached, the valve can be switched to an INJECT positionand the aspired sample volume can thereby be injected into the column 41(FIG. 11 ). This applies in the same way also to the embodiments shownin FIGS. 1 to 8 . The sample volume to the column is preferablyconducted by means of the pump flow and notably, through the sample looppart 52, the port C, the groove Y and the port B.

A control unit (not illustrated) can measure the force that the drive 55has to exert in order to reach a corresponding compression in the sampleloop. The drive 55 can be provided with an integrated sensor (not shown)for this purpose, the signal of which is fed to the control unit. Thecontrol unit can thereby determine the actual pressure in the pumpvolume and thus in the sample loop (the pressure drop in the connectingpieces and the valve is negligibly small) and can regulate it to thedesired value. This applies in the same way also to the embodimentsshown in FIGS. 1 to 8 .

After the aspired sample volume has been completely conveyed from theintake part 44 to the column 41 through the fluid conveyed by the pump40, the valve for decompression of the sample loop can be switcheddirectly into the PRESSURE COMPENSATION position again (FIG. 10 ).

Before the injection valve is moved out of the PRESSURE COMPENSATIONposition back into the LOAD position, the piston 53 is preferably movedinto position C. The pressure in the sample loop is thereby adjusted tothe atmospheric pressure. During this decompression time, the column 41is already connected with the pump 40 in the PRESSURE COMPENSATIONposition of the injection valve 3, due to the hook-shaped design of thegroove X, in order to avoid pressure changes. The conveying path of thepiston 53 from position B to position C can be determined, in the sameway as for the compression, by calculation or by measurement and controlof the pressure. In alternative, the pressure can also be determinedindirectly by means of a force measurement on the piston 53 or the drive55 of the piston.

Once the decompression of the sample loop is completed, the valve 3 isset to the LOAD position. In the process, neither any harmful flowsoccur in the sample pre-compression valve nor any damages on thechromatography column that are caused by pressure changes. The same alsoapplies to the compression step. The piston 53 of the high-pressureresistant sample conveying system 5 can now be driven again to theinitial position A. The excess fluid quantity is disposed through thewaste connection 47, the pressure-less sample needle 42 can thereafterbe moved out of the needle seat of the injection port 45 to thecorresponding sample flask for drawing up the next sample.

The position C in the decompression can also differ from the initialposition C before the compression. If, for example, gradients(time-controlled admixture ratio of the mobile phase) are pumped throughthe column, position Cat the end of the decompression can be a differentone, because the compressibility of the loop content may have changed asapplies.

The mentioned control unit can store the predefined positions A, B, Cand/or path differences between these positions in dependency onparameters of the complete sampler, in particular of the mobile phasecompressibility, elasticity characteristics of the sample loop and thesample conveying system, etc. These positions can then be actuatedspecifically (meaning without a control unit) or they can serve asapproximate values of the initial values for a controlled movement. Todetermine the positions A, B, C or the movement paths for the piston, aswitching process of the sample pre-compression valve 3 can be conductedwithout compression or decompression. By means of a pressure sensor, thepressure drop can then be identified, and the required path andrespectively the relevant position B and respectively C can then bedetermined from it. The values determined this way can then be storedand used for further switching processes in application of a compressionor decompression. A corresponding sensor can also be provided in thepump 40. This is bearing in mind that pumps of this kind for the HPLCalways have a pressure sensor anyway for the control of the conveyedmobile phase. Likewise, the compressibility of the medium, in particularof the mobile phase, can be determined by means of the pump 40. Pumps ofthis kind are designed, for example, as double-piston pumps, whereas theswitching from one piston to another is suitably activated or controlledby means of a pressure sensor and a control unit, in such a way so thata highly constant flow rate results. As the compressibility of themedium must be considered for this switching process, the suitableactuation of the (double-piston) pump when switching from one piston toanother can serve as the basis for determining the compressibility,which can then be supplied to the control unit as information. Thisapplies in the same way also to the embodiments shown in FIGS. 1 to 8 .

With the presented automatic sampler, it is therefore ensured thatbefore the intake part 44 is connected in the liquid path to thechromatography column 41, meaning before the sample pre-compressionvalve 3 is switched to the INJECT position, the sufficiently (high)pressure resistant sample conveying system 5, adjusts the pressure inthe sample loop to the current system pressure in the chromatographycolumn 41 by compression in a special intermediate position of thesample pre-compression valve, namely the PRESSURE COMPENSATION position.

Furthermore, before the sample loop is disconnected for taking in asample volume from a sample tank 43, meaning before the samplepre-compression valve 3 is switched to the LOAD position, the pressurein the sample loop is adjusted to the atmospheric pressure(decompression) by the volume change in the sample conveying system 5,preferably in the same intermediate position of the samplepre-compression valve 3, namely the PRESSURE COMPENSATION position.

FIG. 12 shows the sampler 10 according to the invention with the samplepre-compression valve 3 in the PUMP PURGE position. In this position,the groove X connects the ports A and D, so that the line from the portA to the pump 40, the groove X and the port D can be flushed with theaspired fluid from the pump 40. The flushed fluid as well as solventresidues are disposed out of the waste line 47 in this process.

FIG. 13 shows the sampler 10 according to the invention with the samplepre-compression valve 3 in the FULL PURGE position. In this position,the groove X connects the ports A and C, and the groove Y connects theports D and E, so that the line from the port A to the pump 40, thegroove X, the port C, the feed part 52, the sample needle 42, the needleseat 45, the intake part 44, the sample conveying system 5, the sampleloop part 51, the port E, the groove Y and the port D can be flushedwith the aspired fluid from pump 40. The flushed fluid is purged in thewaste line 47 in this process.

FIG. 14 shows the sampler 10 according to the invention with the samplepre-compression valve 3 in the UNDERPRESSURE position. In this position,the groove X connects the port A with the port C. Furthermore, the portE, the port B and the port D are not connected with any other port inthis position. The sample needle 42 is preferably arranged in the needleseat 45, so that pulling out the piston 53 of the sample conveyingsystem 5 can create an underpressure in the sample loop 51, 44, 52, thegroove X that connects the ports A and C with each other, and theconnecting line from the port A to pump 40. It is possible in this wayto overcome the hydrostatic column of the solvent and to support thepump 40 in aspiring the solvent. In addition, for example, before theFULL PURGE position or the PUMP PURGE position, gas bubbles can beremoved from the device by switching to the UNDERPRESSURE position andthereby creating the underpressure. This preferably takes place whilethe pump 40 has a lower conveying capacity than created by theunderpressure of the sample conveying system or while the pump is shutoff.

FIG. 15 shows a preferred embodiment according to the invention, whereineverything is arranged as shown in FIG. 13 , with the sole exceptionthat the line from the port D is led to a wash port of the needle seatand the waste drain 47 is arranged on the wash port of the needle seat45. This way, the cleaning agent can be conducted into the wash port ofthe needle seat during flushing in the FULL PURGE position and thus, thesample needle 42 is also rinsed from the outside. In the process, theneedle is preferably slightly driven out of the needle seat, so that thecleaning agent can reach the wash port of the needle seat for theexterior cleaning of the sample needle and then be purged from the washport into the waste.

The following reference signs are used in FIGS. 1-15 .

-   -   A Port in stator    -   B Port in stator    -   C Port in stator    -   D Port in stator    -   E Port in stator    -   F Port in stator    -   X Groove in rotor    -   Y Groove in rotor    -   Z Groove in rotor    -   1 Stator    -   2 Rotor    -   3 Sample pre-compression valve    -   5 Sample conducting device    -   10 Sampler    -   40 Solvent pump(s), preferably high-pressure pump(s)    -   41 Chromatography column    -   42 Sample needle    -   43 Sample tank    -   44 Intake part    -   45 Injection port/Needle seat    -   47 Waste line    -   50 Syringe    -   51 Sample loop part    -   52 Sample loop part or feed part    -   53 Movable element    -   55 Controllable drive    -   57 Cleaning pump    -   58 Return valve    -   59 Sample intake/discharge line    -   60 Sample loop    -   61 Solvent bottle    -   62 Wash port    -   63 Waste tank    -   V Volume

What is claimed is:
 1. A sample pre-compression valve for liquidchromatography, the sampler comprising: (a) a stator; and (b) a rotor,which are arranged next to each other along their circular surface andwhich can be rotated against each other along their circular surface,wherein the stator comprises at least five ports A, B, C, D and E andthe rotor comprises at least two grooves X and Y, wherein the grooves Xand Y are configured to respectively connect two of the ports A, B, C, Dand E with each other and wherein the ports can be embodied point-shapedor groove-shaped, characterized in that (ii) the groove X connects theports A and B in a valve position 2, in such a way that there are deadvolumes present in the groove X and so that the groove Y does or doesnot connect ports C and D, and (iii) the groove X connects the ports Aand E with each other in a valve position 3, in such a way so that thereare no dead volumes present in the groove X and so that the groove Ydoes or does not connect the ports B and C.
 2. The samplepre-compression valve of claim 1, wherein there are no dead volumes inthe connecting grooves in valve position
 3. 3. The samplepre-compression valve of claim 1, wherein the groove Y does not connectthe ports C and D in valve position
 2. 4. The sample pre-compressionvalve of claim 1, wherein the groove X connects the ports A and B witheach other in a valve position 1, in such a way that there are no deadvolumes present in the groove X and so that the groove Y does or doesnot connect the ports C and D.
 5. The sample pre-compression valve ofclaim 4, wherein the groove Y connects the ports C and D in valveposition
 1. 6. The sample pre-compression valve of claim 1, wherein thegroove Y connects the ports C and B in valve position
 3. 7. The samplepre-compression valve of claim 1, wherein Position 3 enables an INJECTposition in which the sample is applied on the chromatography column 8.The sample pre-compression valve of claim 1, wherein port A is arrangedat a center of the stator.
 9. The sample pre-compression valve of claim6, wherein ports C and E are arranged on opposites sides relative to theport A and that both are essentially spaced equally far away from theports B and D respectively.
 10. The sample-pre-compression valve ofclaim 1, wherein the ports B, C, D and E are arranged on one or morecircular path(s) around the center of the stator.
 11. The samplepre-compression valve of claim 8, wherein the ports B, C, D and E can bearranged on the same circular path around the center of the stator. 12.The sample pre-compression valve of claim 1, wherein port A isessentially spaced equally far away from the ports B, C, D and E. 13.The sample pre-compression valve of claim 1, wherein the samplepre-compression valve has at most five ports
 14. The samplepre-compression valve of claim 1, wherein the valve has at most the twogrooves X and Y.
 15. The sample pre-compression valve of claim 1,wherein the groove X has a hook-shape.
 16. The sample pre-compressionvalve of claim 1, wherein the groove Y is designed line-shaped orarched, whereas the two end points are respectively arranged on acircular path around the center of the ring-shaped rotor.
 17. The samplepre-compression valve of claim 1, wherein the groove X connects theports A and C with each other in groove X in a valve position 5, in sucha way that no dead volumes are present. And so that the groove Yconnects the ports D and E with each other.
 18. A sampler for liquidchromatography, the sampler comprising: (A) a sample pre-compressionvalve comprising: (a) a stator; and (b) a rotor, which are arranged nextto each other along their circular surface and which can be rotatedagainst each other along their circular surface, wherein the statorcomprises at least five ports A, B, C, D and E and the rotor comprisesat least two grooves X and Y, wherein the grooves X and Y are configuredto respectively connect two of the ports A, B, C, D and E with eachother and wherein the ports can be embodied point-shaped orgroove-shaped, characterized in that (ii) the groove X connects theports A and B in a valve position 2, in such a way that there are deadvolumes present in the groove X and so that the groove Y does or doesnot connect ports C and D, and (iii) the groove X connects the ports Aand E with each other in a valve position 3, in such a way so that thereare no dead volumes present in the groove X and so that the groove Ydoes or does not connect the ports B and C; (B) a sample loop with asample conveying system and a needle seat; (C) a solvent pump; (D) achromatography column; and (E) a sample discharge line.
 19. The samplerof claim 18, wherein the solvent pump and the chromatography column areconnected through grooves X and Y in valve position 3.